The individual symptoms of Parkinson's disease have been described by physicians from the time of Galen, but their occurrence as a syndrome was not recognized until 1817. In that year James Parkinson, a London physician, published an essay in which he argued that several different motor symptoms could be considered together as a group forming a distinctive condition. His observations are interesting not only because his conclusion was correct but also because he made his observations in part at a distance by watching the movements of Parkinsonian victims in the street of London. Parkinson's disease has been called at different times the shaking palsy or its Latin equivalent, paralysis agitans, but received its more common designation from Jean Charcot, who suggested that the disease be renamed to honor James Parkinson's recognition of its essential nature.
Parkinson's disease is fairly common, estimates of its incidence varying from 0.1 to 1.0% of the population. It is also of considerable interest for a number of other reasons. First, the disease seems related to the degeneration of the substantia nigra, and to the loss of the neurotransmitter substance dopamine, which is produced by cells of this region. The disease, therefore, provides an important insight into the role of this brainstem nucleus and its neurotransmitter in the control of movement. Second, because a variety of pharmacological treatments for Parkinson's disease relieve different features of its symptoms to some extent, the disease provides a model for understanding pharmacological treatments of motor disorders in their more general aspects. Third, although Parkinson's disease is described as a disease entity, the symptoms vary enormously among people, thus making manifest the complexity with which the components of movement are organized to produce fluid motion. Fourth, because many of the symptoms of Parkinson's disease strikingly resemble changes in motor activity that occur as a consequence of aging, the disease provides indirect insight into the more general problems of neural changes in aging.
There are three major types of Parkinson's disease: idiopathic, postencephalitic, and drug-induced. Parkinson's diseases may also result from arteriosclerosis, may follow poisoning by carbon monoxide or manganese intoxication, or may result from syphilis or the development of tumors. As is suggested by its name, the cause of idiopathic Parkinson's disease is not known. Its origin may be familiar, or it may be part of the aging process, but it is also widely thought that it might have a viral origin. It most often occurs in people who are over 50 years of age. The postencephalitic form originated in the sleeping sickness that appeared in the winter of 1916-1917 and vanished by 1927. Although the array of symptoms was bewilderingly varied, such that hardly any two patients seemed alike, Constantin von Economo demonstrated a unique pattern of brain damage associated with a virus infection in the brains of patients who had died from the disease. A third of those affected died in the acute stages of sleeping sickness in states either of coma or of sleeplessness. Although many people seemed to completely recover from the sickness, most subsequently developed neurological or psychiatric disorders and parkinsonism. The latency between the initial and subsequent occurrences of the disease has never been adequately explained. Searches for viral particles or virus-specific products in Parkinson patients have revealed no evidence of viral cause. The third major cause of Parkinson's disease is more recent, and is associated with ingestion of various drugs, particularly major tranquilizers that include reserpine and several phenothiazine and butyrophenone derivatives. The symptoms are usually reversible, but they are difficult to distinguish from those of the genuine disorder.
Recently it has been found that external agents can cause symptoms quite rapidly. Langston and coworkers have reported that a contaminant of synthetic heroin, MPTP, when taken by drug users is converted into MPP+, which is extremely toxic to dopamine cells. A number of young drug users were found to display a complete parkinsonian syndrome after using contaminated drugs. This finding has suggested that other substances might cause similar effects. Demographic studies of patient admission in the cities of Vancouver and Helsinki show an increase in the incidence of patients getting the disease at ages younger than 40. This has raised the suggestion that water and air might contain environmental toxins that work in a fashion similar to MPTP.
Although Parkinsonian patients can be separated into clinical groups on the basis of cause of the disease, it is nevertheless likely that the mechanisms producing the symptoms have a common origin. Either the substrantia nigra is damaged, as occurs in idiopathic and postencephalitic cases, or the activity of its cells is blocked or cells are killed, as occurs in drug-induced parkinsonism. The cells of the substantia nigra contain a dark pigment in Parkinson's disease that is depigmented by degeneration of the melatonin-containing neurons of the area. The cells of the substantia nigra are the point of origin of fibers that go to the basal ganglial frontal cortex and to the spinal cord. The neurotransmitter at the synapses of these projections is dopamine. It has been demonstrated by bioassay of the brains of deceased parkinsonian patients, and by analysis of the major metabolite of dopamine, homovanallic acid, which is excreted in the urine, that the amount of brain dopamine is reduced by over 90% and is often reduced to undetectable amounts. Thus, the cause of Parkinson's disease has been identified with some certainty as a lack of dopamine or, in drug-induced cases, with a lack of dopamine action.
Accordingly, pharmaceuticals and methods of treatment for treatment or prophylaxis of Parkinson's disease are needed.